JCEM case reports最新文献

A defect in the canonical Wnt-β-catenin pathway may lead to reduced bone strength and increased fracture risk. Sclerostin is a key inhibitor of this pathway by binding to low-density lipoprotein (LDL) receptor-related protein (LRP)-5/6, thereby reducing bone formation. The effectiveness of romosozumab, a human monoclonal antibody that binds sclerostin and prevents this inhibitory effect, has been questioned in patients with inactivating genetic variants in LRP5 or LRP6. We present a 67-year-old woman with severe osteoporosis with 4 grade 2 vertebral fractures due to a heterozygous pathogenic variant in LRP5. She was treated with romosozumab for 1 year, after which a routine follow-up spine x-ray revealed 5 new vertebral fractures, despite a strong increase in bone mineral density (BMD) (lumbar spine [LS] + 58%; femur neck [FN] + 23%), although overestimated at LS because of the vertebral fractures. This suggests that in patients with loss-of-function LRP5 variants, romosozumab is able to increase BMD. However, it is unclear whether the progressive vertebral fractures are due to the severe osteoporosis in relation to the start of romosozumab or a diminished responsiveness related to her LRP5 variant. Further evaluation is needed on the effect of romosozumab on BMD and fracture outcomes in patients with a likely defective LRP5/6 receptor.

Lymphocytic infundibuloneurohypophysitis (LINH) is a disease with an etiology involving an autoimmune mechanism, characterized by lymphocytic inflammation of the posterior pituitary and infundibular stalk, resulting in arginine vasopressin deficiency. It is difficult to distinguish from pituitary neoplasm or infiltrative diseases, and biopsy is necessary for a definitive diagnosis, but this is highly invasive. In children, it is especially important to distinguish LINH from tumors such as germ cell tumors. Recently, the usefulness of anti-rabphilin-3A antibody as a serum marker for LINH has been reported. To date, only a limited number of pediatric cases have been reported. We present a 4-year-old boy with arginine vasopressin deficiency. Magnetic resonance imaging of the head showed thickening of the pituitary stalk without a posterior pituitary bright spot, and anti-rabphilin-3A antibody was positive. Consequently, pituitary biopsy was not performed because of the strong suspicion of LINH. Five months after symptom onset, the pituitary stalk thickening had resolved. This case represents the first report of probable or definitive LINH with anti-rabphilin-3A antibody positivity in a 4-year-old child, making it the youngest positive case reported to date. Our case highlights the importance of noninvasive approaches and careful follow-up to avoid invasive interventions for children with LINH.

46,XY sex reversal 11 (SRXY11) is a rare and recently identified form of 46,XY difference in sexual development (DSD), caused by variants in the DEAH-Box Helicase 37 gene (DHX37). DHX37 is crucial for ribosome biogenesis, but its specific role in gonadal development remains unclear. The genital phenotype varies widely, ranging from typical female to typical male. We present a 46,XY infant with prenatal ultrasound findings of atypical genitalia. Amniotic fluid gene analysis revealed a known heterozygous pathogenic variant in DHX37, p.R308Q (c.923G>A), confirmed postnatally. The patient was born with markedly undervirilized genitalia with posteriorly fused labioscrotal folds, a single introitus, no clitoromegaly, and nonpalpable gonads. Laboratory evaluation at multiple points showed undetectable anti-Müllerian hormone (AMH) and inhibin B levels, elevated gonadotropin levels, and negligible testosterone levels. Clinical course was complicated by urine retention in the vagina and uterus and hydronephrosis requiring catheterization. Endoscopy revealed a urogenital sinus with separate urethral and vaginal openings and 2 cervices leading into 2 separate uteri suggestive of a bicornuate bicollis uterus. Laparoscopy revealed 2 intra-abdominal gonads adjacent to the fallopian tubes. Evidence for inheritance, penetrance, genotype-phenotype correlation, and risk of malignancy in SRXY11 is limited to case reports.

Routine serum studies in a female patient with sustained prediabetic glycated hemoglobin A_1c (HbA_1c) levels, controlled on metformin, yielded an unexpected finding: an elevated HbA_1c value of ≥14.9% (≥139 mmol/mol) (normal reference range, <5.7% to <39 mmol/mol). Estimated average glucose (EAG) (normal reference range, <126 mg/dL to <7 mmol/L) is a linearly corresponding blood glucose value calculated from HbA_1c measurements that reflects the average glycemic status over the preceding 3 months. Caution must be used when the EAG provided by the HbA_1c does not align with blood glucose values obtained around the same period. Our patient carries a rare heterozygous pathogenic variant affecting the β subunit called hemoglobin Graz (Hb Graz), characterized by a histidine for leucine substitution, resulting in clinically silent Hb abnormalities. Individuals without diabetes carrying the Hb Graz pathogenic variant exhibit significantly higher HbA_1c values when analyzed by high-performance liquid chromatography. Alternative methods of quantifying glycemic control are suggested if the possibility of a confounding variable exists, such as when a HbA_1c-blood glucose mismatch occurs or unexplainable HbA_1c levels are detected.

Androgen secretion by testicular germ-cell tumors (GCTs) appears to be markedly rare and likely underreported in the literature. This case study highlights a patient with such a rare tumor, underscoring a notable and yet easily avoidable diagnostic oversight in one of the most prevalent cancers among men. We advocate for increased vigilance and the inclusion of specific symptomatic screening for hyperandrogenism of select patients in existing guidelines and, where appropriate, the implementation of standardized hormonal laboratory analyses in both pre- and post-orchidectomy assessments. These measures could enhance the reporting of cases, standardize care, and improve understanding of the underlying mechanisms of these rare tumors. Finally, future studies should explore the implications of androgen secretion for the prognosis and treatment of GCTs.

Pheochromocytoma and paraganglioma (PPGL) are rare chromaffin-cell tumors producing adrenaline and/or noradrenaline, or solely dopamine. A 52-year-old man presenting with hypertension (141/79 mm Hg) and weight loss (10 kg in 6 months) was admitted to our hospital. Computed tomography revealed a massive right adrenal mass (150 mm) with partial necrosis, accompanied by multiple liver nodules. These nodules showed a high signal intensity on T2-weighted magnetic resonance imaging. Subsequently, a diagnosis of PPGL was made based on elevated urinary excretion of adrenaline (355 µg/day [1937 nmol/day]; normal range: 3.4-26.9 µg/day; 18-146 nmol/day), noradrenaline (1690 µg/day [9989 nmol/day]; normal range: 48.6-168.4 µg/day; 287-995 nmol/day), and dopamine (53 000 µg/day [258 322 nmol/day]; normal range: 365-961.5 µg/day; 1779-4686 nmol/day). The ¹²³I-metaiodobenzylguanidine scintigraphy and fluorodeoxyglucose positron emission tomography scan showed heterogenous uptake among the adrenal and the liver foci, respectively. Clustering analysis of previous PPGL cases highlighted the unique catecholamine profile of this case. These findings suggest a possibility that internodular heterogeneity between primary and metastatic foci on nuclear imaging may indicate varying differentiation grades and resultant catecholamine secretion. Further studies will be needed to verify these results and confirm this hypothesis.

Maturity-onset diabetes of the young (MODY) represents 1% to 5% of patients with diabetes mellitus (DM), and numerous genes associated with MODY have been identified. While mutations of the insulin gene (INS) are known to cause permanent neonatal DM, rare disease-causing variants have also been found in MODY. These patients demonstrate variable clinical phenotypes-from milder forms requiring lifestyle or oral agent interventions to severe forms requiring lifelong insulin. We present a case of MODY arising from a novel disease-causing INS variant, in an adolescent with atypical features. He was obese with clinical evidence of insulin resistance, diagnosed with DM through opportunistic oral glucose tolerance testing. He developed symptomatic hyperglycemia with worsening glycemic trend, requiring treatment with high-dose insulin and metformin. After 2.5 years, his glycemic profile normalized following weight loss, and pharmacotherapy was discontinued. Targeted gene testing revealed a de novo novel missense variant in exon 2 of the INS gene (p.His29Tyr), confirmed using bidirectional Sanger sequencing. Insulin resistance in patients with MODY can worsen their clinical course and increase risks of long-term complications. Management of these patients should be individualized. This case highlights the utility of genetic testing in diagnosing uncommon and variable forms of MODY, particularly those with atypical features.

As the leading cause of hyperthyroidism, Graves disease (GD) does not often present with its classical triad of pretibial myxedema, goiter, and exophthalmos but instead is often recognized by various manifestations such as tachycardia, weight loss, jaundice, or dermatopathy and requires utmost clinical vigilance. Three treatment modalities for GD exist as antithyroid drugs (ATDs), radioactive iodine (RAI), and surgery, but each bears its own serious side effects. Furthermore, there have been several reports in the literature about ATD resistance that can complicate management. We describe a rare complex case of methimazole (MMI)-resistant GD in a 58-year-old woman with multiple comorbidities including heart failure, atrial fibrillation, liver cirrhosis, and hypertension. She presented with an initial complaint of diffuse swelling and was found to have severe thyrotoxicosis. Despite high doses of MMI, her thyroid function remained significantly elevated. Thyroid uptake and scan while on MMI showed high radioactive iodine uptake. After receiving RAI therapy, her thyroid function and bilirubin improved markedly, liver enzymes remained stable, and anasarca responded to diuretics. This case highlights the challenges in managing resistant GD and emphasizes the necessity of personalized treatment plans.

Patients with intermediate-risk thyroid cancers may undergo treatment with radioactive iodine-131 (I-131). They often undergo a pretreatment diagnostic iodine scan that typically shows areas of physiological uptake in the stomach, bladder, parotid glands as well as thyroid-remnant uptake and sites of metastatic disease. A 48-year-old woman with intermediate-risk papillary thyroid cancer with metastases to lateral compartment lymph nodes was found to have increased retention of iodine in the medial portion of her left orbit on the diagnostic scan. This was suggestive of preexisting nasolacrimal duct stenosis leading to retention of secretions in the lacrimal sac, raising concerns that the I-131 used in treatment would have delayed clearance that could further damage her lacrimal sac and eye. In consultation with ophthalmology, the patient received pretreatment azelastine and prednisolone drops and underwent treatment with radioactive iodine followed by saline lacrimal irrigation. Though she had subsequent eye pain and swelling necessitating repeated irrigation, the patient was able to undergo treatment for her papillary thyroid cancer and retained full function of her eye. This case highlights an approach that could be used for patients with nasolacrimal duct stenosis in whom radioactive iodine treatment is deemed beneficial.